CEGT_CRYNH
ID CEGT_CRYNH Reviewed; 450 AA.
AC J9W453; Q58FH5;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2012, sequence version 1.
DT 25-MAY-2022, entry version 43.
DE RecName: Full=Ceramide glucosyltransferase {ECO:0000250|UniProtKB:Q16739};
DE EC=2.4.1.80 {ECO:0000269|PubMed:16741577};
DE AltName: Full=GLCT-1;
DE AltName: Full=Glucosylceramide synthase {ECO:0000303|PubMed:16741577};
DE Short=GCS {ECO:0000303|PubMed:16741577};
DE AltName: Full=UDP-glucose ceramide glucosyltransferase;
DE AltName: Full=UDP-glucose:N-acylsphingosine D-glucosyltransferase;
GN Name=GCS1 {ECO:0000303|PubMed:16741577}; ORFNames=CNAG_05583;
OS Cryptococcus neoformans var. grubii serotype A (strain H99 / ATCC 208821 /
OS CBS 10515 / FGSC 9487) (Filobasidiella neoformans var. grubii).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Tremellomycetes;
OC Tremellales; Cryptococcaceae; Cryptococcus;
OC Cryptococcus neoformans species complex.
OX NCBI_TaxID=235443;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND
RP DISRUPTION PHENOTYPE.
RC STRAIN=H99 / ATCC 208821 / CBS 10515 / FGSC 9487;
RX PubMed=16741577; DOI=10.1172/jci27890;
RA Rittershaus P.C., Kechichian T.B., Allegood J.C., Merrill A.H. Jr.,
RA Hennig M., Luberto C., Del Poeta M.;
RT "Glucosylceramide synthase is an essential regulator of pathogenicity of
RT Cryptococcus neoformans.";
RL J. Clin. Invest. 116:1651-1659(2006).
RN [2]
RP ERRATUM OF PUBMED:16741577.
RX DOI=10.1172/JCI27890C1;
RA Rittershaus P.C., Kechichian T.B., Allegood J.C., Merrill A.H. Jr.,
RA Hennig M., Luberto C., Del Poeta M.;
RL J. Clin. Invest. 117:1450-1450(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=H99 / ATCC 208821 / CBS 10515 / FGSC 9487;
RX PubMed=24743168; DOI=10.1371/journal.pgen.1004261;
RA Janbon G., Ormerod K.L., Paulet D., Byrnes E.J. III, Yadav V.,
RA Chatterjee G., Mullapudi N., Hon C.-C., Billmyre R.B., Brunel F.,
RA Bahn Y.-S., Chen W., Chen Y., Chow E.W.L., Coppee J.-Y., Floyd-Averette A.,
RA Gaillardin C., Gerik K.J., Goldberg J., Gonzalez-Hilarion S., Gujja S.,
RA Hamlin J.L., Hsueh Y.-P., Ianiri G., Jones S., Kodira C.D., Kozubowski L.,
RA Lam W., Marra M., Mesner L.D., Mieczkowski P.A., Moyrand F., Nielsen K.,
RA Proux C., Rossignol T., Schein J.E., Sun S., Wollschlaeger C., Wood I.A.,
RA Zeng Q., Neuveglise C., Newlon C.S., Perfect J.R., Lodge J.K., Idnurm A.,
RA Stajich J.E., Kronstad J.W., Sanyal K., Heitman J., Fraser J.A.,
RA Cuomo C.A., Dietrich F.S.;
RT "Analysis of the genome and transcriptome of Cryptococcus neoformans var.
RT grubii reveals complex RNA expression and microevolution leading to
RT virulence attenuation.";
RL PLoS Genet. 10:E1004261-E1004261(2014).
CC -!- FUNCTION: Catalyzes the final step in the biosynthesis of the membrane
CC lipid glucosylceramide (GluCer), the transfer of glucose to ceramide.
CC Glucosylceramides play important roles in growth, differentiation and
CC pathogenicity. Essential factor in determining the success of fungal
CC infection by regulating survival of yeast cells during the initial
CC colonization of the host lung. {ECO:0000269|PubMed:16741577}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acylsphing-4-enine + UDP-alpha-D-glucose = a beta-D-
CC glucosyl-(1<->1')-N-acylsphing-4-enine + H(+) + UDP;
CC Xref=Rhea:RHEA:12088, ChEBI:CHEBI:15378, ChEBI:CHEBI:22801,
CC ChEBI:CHEBI:52639, ChEBI:CHEBI:58223, ChEBI:CHEBI:58885; EC=2.4.1.80;
CC Evidence={ECO:0000269|PubMed:16741577};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000305|PubMed:16741577}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q9R0E0}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- DOMAIN: The D1, D2, D3, (Q/R)XXRW motif is a critical part of the GCS
CC active site, involved in catalysis and UDP-sugar binding.
CC {ECO:0000250|UniProtKB:Q9R0E0}.
CC -!- DISRUPTION PHENOTYPE: Results in complete loss of glucosylceramides
CC (GluCers) in mutant cells. {ECO:0000269|PubMed:16741577}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 2 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY956317; AAX55972.1; -; mRNA.
DR EMBL; CP003833; AFR99010.1; -; Genomic_DNA.
DR RefSeq; XP_012053860.1; XM_012198470.1.
DR AlphaFoldDB; J9W453; -.
DR EnsemblFungi; AFR99010; AFR99010; CNAG_05583.
DR GeneID; 23888885; -.
DR VEuPathDB; FungiDB:CNAG_05583; -.
DR HOGENOM; CLU_030898_1_0_1; -.
DR BRENDA; 2.4.1.80; 1723.
DR UniPathway; UPA00222; -.
DR PHI-base; PHI:693; -.
DR Proteomes; UP000010091; Chromosome 14.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0008120; F:ceramide glucosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0102769; F:dihydroceramide glucosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0006665; P:sphingolipid metabolic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR025993; Ceramide_glucosylTrfase.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR PANTHER; PTHR12726; PTHR12726; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
PE 1: Evidence at protein level;
KW Glycosyltransferase; Golgi apparatus; Lipid metabolism; Membrane;
KW Sphingolipid metabolism; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..450
FT /note="Ceramide glucosyltransferase"
FT /id="PRO_0000434809"
FT TOPO_DOM 1..8
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..337
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9R0E0"
FT TRANSMEM 338..358
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 359..361
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 362..382
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 383..401
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 402..422
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 423..450
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT MOTIF 96
FT /note="D1"
FT /evidence="ECO:0000305"
FT MOTIF 148
FT /note="D2"
FT /evidence="ECO:0000305"
FT MOTIF 286
FT /note="D3"
FT /evidence="ECO:0000305"
FT MOTIF 323..327
FT /note="(Q/R)XXRW"
FT /evidence="ECO:0000305"
FT ACT_SITE 286
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9R0E0"
SQ SEQUENCE 450 AA; 49721 MW; A5227128E9C45C9A CRC64;
MSDSGTLSLI GGIVFLVLWV VVWSICLLGW RTARIRYAHP NIPSRLSKLP VSSAPGVTII
RPLCGLDQNL YNTLESVMKL DYPKFEVIFA VQDEKDEALP VVNMVMEKYP EVEAKVIIDS
RKVGVNPKVN NLMTPFQEAK YDLLWILDST CSVLPGTLGR SVEAFFSNTS STASPYDPES
SPLLSISDDV RKPPIAGEVG LVHQVPIAVC YQKTWGSLIE QAYLNTTHAK MYLAINATSI
DSCVVGKSCM YSRDNISHLT TPSPSLRSLP DPPSGLAGFG PFLAEDNMIG LSLWHELKLK
HAMTSDVVLD FIGSLSVRDY INRRVRWIRV RKKMTLAATL LEPLTESIIS GLYGAWAISR
LLGGNILPLF LLHMAAWISV DISTKRALET NIKGIGPPES KVTFLMAWAA RECLALPIWM
LAMTSSEVVW RGQKYKIIAS GEAIRLGDRN
